61182017
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`Sticky Conners Wishing Drugs I In the Pipeline
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`Cell analysis
`Time for a change
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`June 28 2017
`r1 Eastern b an
`T CET
`IA 3 in
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`ETHERLI
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`Science
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`AAAS
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`Sponsored by
`Tie rtrici Fisher Scientific
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`EP EL NE
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`Derek Lowes commentary on drug discovery and the pharma industry An editorially independent Nog from the publishers of Science Translational Medicine
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`By Conk Lam
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`Sticky Containers Vanishing Drugs
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`By Derek Lowe I August 29 2008
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`Theres no end to the variables that can kick your data around in drug discovery If you concentrate completely on all
`the things that could go
`wrong though youll be too terrified to run any useful experiments You have to push on but stay alert Its like medical practice most of the
`time you dont have to worry about most of the possibilities but you need to recognize the odd ones when they show up
`One particular effect gets rediscovered from time to time and Ive just recently had to take it
`into account myself the material that your vials
`and wells are made out of Thats generally not a consideration for organic chemists since we work mostly in glass and on comparatively
`large scale There are some cases where glass specifically the free OH groups on Its surface can mess up really sensitive compounds but
`in drug discovery we try not to work with things that are that temperamental
`But when you move to the chemistrybiology interface things change Material effects are pretty wellknown
`among pharrnacokinetics
`people for example although not all medicinal chemists are aware of them The reason is that PK samples blood plasma tissue tend to
`have very small amounts of the desired analyte in them inside a sea of proteins and other gunk If youre going down to nanograms or less
`of the substance of interest it doesnt take much to mess up your data
`And as it turns out different sorts of plastics will bind various compounds to widely varying degrees Taxol OK taxotere is a notorious
`example sticking to the sides of various containers like crazy And you never know when youre going to run into one of those yourself I
`know of a drug discovery project whose PK numbers were driving everyone crazy weirdly variable and mostly suggesting physically
`impossible levels of drug clearance until they figured out that this was the problem If you took a stock solution of the compound and ran it
`though a couple of dilutions while standing in the standard plastic vials nothing was left Wash the suckers out with methanol though and
`voila
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`Heres a paper which suggests that polystyrene can be a real offender and from past experience I can tell you to look out for polypropylene
`especially the cheap stuff You wont notice anything until you get way down there to the tiny amounts
`but if thats where youre working
`in mind
`youd better keep it
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`24 comments on Sticky Containers Vanishing Drugs
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`HelicalZz says
`August 292008 at 847 am
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`Two words method validation
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`Not full blown but linearity and limit of detection just gotta be done First
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`juniorprof says
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`htlpbIcgssciencemagorgfpipelinelarchives20080829Isticky
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`containers
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`vanishingckugs
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